The present invention relates to the field of mass spectrometry and in particular to apparatus and methods for ion-surface interactions within mass analyzers.
Mass spectrometers are used to analyze sample substances (containing elements or compounds or mixtures of elements or compounds) by measuring the mass to charge of ions produced from a sample substance in an ion source. A number of types of ion sources that can produce ions from solid, liquid or gaseous sample substrates have been combined with mass spectrometers. Ions can be produced in vacuum using ion sources, including, but not limited to, Electron Ionization (EI), Chemical Ionization (CI, Laser Desorption LD), Matrix Assisted Laser Desorption (MALDI), Fast Atom Bombardment (FAB), Field Desorption (FD) or Secondary Ion Mass Spectrometry (SIMS). Alternatively, ions can be produced at or near atmospheric pressure using ion sources, including, but not limited to, Electrospray (ES), Atmospheric Pressure Chemical Ionization (APCI) or Inductively Coupled Plasma (ICP). Ion sources that operate at intermediate vacuum pressures such as Glow Discharge Ion Sources have also been used to generate ions for mass spectrometric analysis. Ion sources that operate in vacuum are generally located in the vacuum region of the mass spectrometer near the entrance to the mass analyzer to improve the efficiency of ion transfer to the detector. Ion sources that produce ions in vacuum have also been located outside the region near the mass spectrometer entrance. The ions produced in a location removed from the mass analyzer entrance must be delivered to the entrance region of the mass spectrometer prior to mass analysis. Atmospheric or intermediate pressure ion sources are configured to deliver ions produced at higher pressure into the vacuum region of the mass analyzer. The geometry and performance of the ion optics used to transport ions from an ion source into the entrance region of a given mass analyzer type can greatly affect the mass analyzer performance. This is particularly the case with Time-Of-Flight mass analyzers, in which the initial spatial and energy distribution of the ions pulsed into the flight tube of a Time-Of-Flight mass analyzer affects the resulting mass to charge analysis resolution and mass accuracy.
Mass analysis conducted in a Time-Of-Flight mass (TOF) spectrometer is achieved by accelerating or pulsing a group of ions into a flight tube under vacuum conditions. During the flight time, ions of different mass to charge values spatially separate prior to impacting on a detector surface. Ions are accelerated from a first acceleration or pulsing region and may be subject to one or more acceleration and deceleration regions during the ion flight time prior to impinging on a detector surface. Multiple ion accelerating and decelerating stages configured in Time-Of-Flight mass spectrometers aid in compensating or correcting for the initial ion spatial and energy dispersion of the initial ion population in the first ion pulsing or accelerating region. The most common lens geometry used in the first TOF ion pulsing or accelerating region is two parallel planar electrodes with the electrode surfaces oriented perpendicular to the direction of ion acceleration into the Time-Of-Flight tube. The direction of the initial ion acceleration is generally in a direction parallel with the TOF tube axis. A linear uniform electric field is formed in the gap between the two parallel planar electrodes when different electrical potentials are applied to the two electrodes. The planar electrode positioned in the direction of ion acceleration into the TOF tube is generally configured as a highly transparent grid to allow ions to pass through with minimal interference to the ion trajectories. To maximize the performance of a Time-Of-Flight mass analyzer, it is desirable to initiate the acceleration of ions in the pulsing region with all ions initially positioned in a plane parallel with the planar electrodes and initially having the same initial kinetic energy component in the direction of acceleration. Consequently, when ions are generated in or transported into the initial accelerating or pulsing region of a Time-Of-Flight mass analyzer, conditions are avoided which lead to ion energy or spatial dispersion at the initiation of ion acceleration into the Time-Of-Flight tube drift region. As a practical matter, a population of gaseous phase ions located in the pulsing region will have a non-zero spatial and kinetic distribution prior to pulsing into a Time-Of-Flight tube drift region. This non zero spatial and kinetic energy spread may degrade Time-Of-Flight mass to charge analysis resolution, sensitivity and mass measurement accuracy. In one aspect of the present invention, the spatial and energy spread of an ion population is minimized prior to accelerating the population of ions into a Time-Of-Flight tube drift region.
When ion spatial and energy spread can not be avoided in the TOF pulsing or first accelerating region, it is desirable to have the ion energy and spatial distributions correlated so that both can be compensated and corrected for during the ion flight time prior to hitting the detector. A correlation between the ion kinetic energy component in the TOF axial direction and spatial spread can occur in the TOF pulsing region when spatially dispersed ions with a non random TOF axial kinetic energy component are accelerated in a uniform electric field formed between two parallel electrodes. Wiley et. al., The Review of Scientific Instruments 26(12):1150-1157 (1955) described the configuration and operation of a second ion accelerating region to refocus ions of like mass to charge along the TOF flight path that start their acceleration with a correlated spatial and energy spread. Electrode geometries in the TOF tube and voltages applied to these electrodes can be varied with this technique to position the focal plane of a packet of ions of the same mass to charge value at the detector surface to achieve maximum resolution. The Wiley-McClaren focusing technique improves resolution when ions occupying a finite volume between two parallel plate electrodes are accelerated. In a uniform electric accelerating field, ions of the same m/z value located closer to the repelling electrode will begin their acceleration at a higher potential than an ion of the same m/z initiating its acceleration at a position further from the repelling electrode. The ion that starts its acceleration nearer to the repelling electrode surface at a higher potential, must travel further than the slower ion which starts its acceleration at a lower potential closer to the extraction grid or electrode. At some point in the subsequent ion flight, the faster ion will pass the slower ion of the same m/z value. By adding a second accelerating region, the location of the point where the ions having the same mass to charge value pass and hence are xe2x80x9cfocusedxe2x80x9d in a plane, can be optimized to accommodate a desired flight time and flight tube geometry. The focal point occurring in the first field free region in the TOF drift tube can be xe2x80x9creflectedxe2x80x9d into a second field free region using an ion mirror or reflector in the ion flight path.
Variations in ion flight time can also be caused by initial ion velocity components not correlated to the spatial spread. This non-correlated ion kinetic energy distribution can be compensated for, to some degree, by the addition of an ion reflector or mirror in the ion flight path. Ions of the same m/z value with higher kinetic energy in the TOF axial direction will penetrate deeper into the decelerating field of an ion reflector prior to being re-accelerated in the direction of the detector. The ion with higher kinetic energy experiences a longer flight path when compared to a lower energy ion of the same m/z value. Subjecting an ion to multiple accelerating and decelerating electric fields allows operation of a TOF mass analyzer with higher order focusing to improve resolution and mass accuracy measurement. Configuration and operation of an Atmospheric Pressure Ion Source Time-Of-Flight mass analyzer with higher order focusing is described by Dresch in U.S. patent application Ser. No. 60/021,184. Higher order focusing corrections can not entirely compensate for initial ion kinetic energy spread in the TOF axial direction that is not correlated with ion spatial spread in the initial pulsing or ion acceleration region. Also, higher order focusing can not entirely compensate for ion energy or spatial spreads which occur during ion acceleration, deceleration or field free flight due to ion fragmentation or ion collisions with neutral background molecules. A ion kinetic energy distribution not correlated to the ion spatial distribution can occur when ionization techniques such as MALDI are used. In MALDI ionization, the sample-bearing surface is located in the initial acceleration region of a Time-Of-Flight mass spectrometer. A laser pulse impinging on a sample surface, in a MALDI ion source, creates a burst of neutral molecules as well as ions in the initial accelerating region of a Time-Of-Flight mass analyzer. Ion to neutral molecule collisions can occur during ion extraction and acceleration into the TOF drift tube resulting in an ion kinetic energy spread, ion fragmentation, degradation of resolution and errors in mass to charge measurement. This problem increases if structural information via ion fragmentation is desired using MALDI Time-Of-Flight mass analysis. Higher energy laser pulses used in MALDI to increase the ion fragmentation also result in increased neutral molecule ablation from the target surface. Even in the absence of ion-neutral collisions, ions generated from the target surface have an initial velocity or kinetic energy distribution that is not well correlated to spatial distribution in the first ion acceleration region. This initial non-correlated kinetic distribution of the MALDI generated ion population can degrade resolution, and mass accuracy performance in Time-Of-Flight mass analysis.
A technique, termed delayed extraction, has been developed where the application of an electric field to accelerate ions into the TOP drift tube is delayed after the MALDI laser pulse is fired to allow time for the neutral gas to expand, increasing the mean free path prior to ion acceleration. By applying a small reverse accelerating field during the MALDI laser pulse and delaying the acceleration of ions into the Time-Of-Flight tube drift region, as described by Vestal et. al. in U.S. Pat. No. 5, 625,184, some portion of the low m/z ions can be eliminated. A portion of the low m/z ions, primarily matrix related ions, created in the MALDI process are accelerated back to the sample surface and neutralized when the reverse electric field is applied. A portion of the slower moving higher mass to charge ions do not return to the target surface as rapidly as the lower molecular weight ions when the reverse accelerating field is applied. After an appropriate delay, these higher molecular weight ions may be forward accelerated into the TOP tube drift region by switching the electric field applied between the two electrodes in the first ion acceleration region. Delayed extraction also allows many of the fast fragmentation processes to occur prior to accelerating ions into the Time-Of-Flight tube drift region, resulting in improved mass to charge resolution and mass accuracy measurements for the ions produced in fast fragmentation processes. The delayed extraction technique reduces the ion energy deficit which can occur due to ion-neutral collisions in the first accelerating region but does not entirely eliminate it, particularly with higher energy laser pulses. Also, delayed extraction is effective in improving MALDI Time-Of-Flight performance when lasers with longer pulse durations are used. However, even with delayed extraction, there is a limit to the length of delay time, the magnitude of the reverse field during the delay period, the laser power used and the duration of a laser pulse before overall sensitivity or Time-Of-Flight performance is degraded. The delayed extraction technique requires a balancing of several variables to achieve optimal performance, often with compromises to the Time-Of-Flight mass analysis performance over all or some portion of the mass to charge spectrum generated. The present invention improves the performance of MALDI Time-Of-Flight without imposing the restrictions or limitations of delayed extraction techniques and provides more uniform Time-Of-Flight mass analysis performance over a wider mass to charge range.
When ions are generated in an ion source positioned external to the Time-Of-Flight pulsing or first acceleration region, a technique termed xe2x80x9corthogonalxe2x80x9d pulsing has been used to minimize effects of the kinetic energy distribution of the initial ion beam. This orthogonal pulsing technique first reported by The Bendix Corporation Research Laboratories Division, Technical Documentary Report No. ASD-TDR-62-644, Part 1, April 1964, has become a preferred technique to interface external ion sources, particularly Atmospheric Pressure Ionization Sources, with Time-Of-Flight mass analyzers. The ion beam produced from an Atmospheric Pressure Ion Source (API) or an ion source that operates in vacuum, is directed into the gap between the two parallel planar electrodes defining the first accelerating region of the TOF mass analyzer. The primary ion beam trajectory is directed to traverse the gap between the two parallel planar electrodes in the TOF first accelerating region substantially orthogonal to axis of the direction of ion acceleration into Time-Of-Flight tube. With the orthogonal pulsing technique, any kinetic energy distribution in the primary ion beam is not coupled to the ion velocity component oriented in the direction of ion acceleration into the Time-Of-Flight tube drift region. The primary ion beam kinetic energy spread oriented along the beam axis only affects the location of ion impact on the planar detector surface, not the ion arrival time at the detector surface. Apparatus and methods have been developed to improve the duty cycle TOF mass analyzers configured with linear or orthogonal pulsing geometries.
Dresch et. al. in U.S. Pat. No. 5,689,111 describe an apparatus and method for improving the duty cycle and consequently the sensitivity of a Time-Of-Flight mass analyzer. Ions contained in a continuous ion beam delivered from an atmospheric pressure ion source into a multipole ion guide, are trapped in the multipole ion guide and selectively released from the ion guide exit into the TOF pulsing region. This apparatus and technique delivers ion packets into the pulsing or first acceleration region of a TOF mass analyzer from a continuous ion beam with higher efficiency and less ion loss than can be achieved with a continuous primary ion beam delivered directly into the TOF pulsing region. Ion trapping of a continuous ion beam in an ion guide effectively integrates ions delivered in the primary ion beam between TOF pulses. When this apparatus and technique is applied to an orthogonal pulsing TOF geometry, portions of the mass to charge range can be prevented from being accelerated into the Time-Of-Flight drift region, reducing unnecessary detector channel dead time, resulting in improved sensitivity and dynamic range. Operation with the orthogonal pulsing technique has provided significant Time-Of-Flight mass analysis performance improvements when compared with the performance using in-line ion beam pulsing techniques. Even with orthogonal pulsing, it is not always possible to achieve optimal primary ion beam characteristics in the pulsing region whereby all orthogonal velocity components are eliminated or spatially correlated. One embodiment of the invention combines orthogonal ion beam introduction into the TOF pulsing region with ion collection on a surface prior to pulsing the surface collected ion population into the TOF tube drift region. The spatial and energy compression of the ion population on the collecting surface prior to pulsing into the TOF tube drift region improves the Time-Of-Flight performance and analytical capability.
The orthogonal pulsing technique has been configured in hybrid or tandem mass spectrometers that include Time-Of-Flight mass analysis. Two or more individual mass analyzers are combined in tandem or hybrid TOF mass analyzers to achieve single or multiple mass to charge selection and fragmentation steps followed by mass analysis of the product ions. Identification and/or structural determination of compounds is enhanced by the ability to perform MS/MS or multiple MS/MS steps (MS/MSn) in a given chemical analysis. It is desirable to control the ion fragmentation process so that the required degree of fragmentation for a selected ion species can be achieved in a reproducible manner. Time-Of-flight mass analyzers have been configured with magnetic sector, quadrupole, ion trap and additional Time-Of-Flight mass analyzers to perform mass selection and fragmentation prior to a final Time-Of-Flight mass analysis step. Gas phase Collisional Induced Dissociation (CID) and Surface Induced Dissociation (SID) techniques have been used to selectively fragment gas phase ions prior to TOF mass analysis or coupled to the ion flight path in the Time-Of-Flight tube. CID ion fragmentation has been the most widely used of the two techniques. Magnetic sector mass analyzers have been configured to perform mass to charge selection with higher energy CID fragmentation of mass to charge selected ions to aid in determining the structure of compounds. Lower energy CID fragmentation achievable in quadrupoles, ion traps and Fourier Transform mass analyzers, although useful in many analytical applications, may not provide sufficient energy to effectively fragment all ions of interest. High energy CID fragmentation can yield side chain cleavage fragment ion types known as w type fragments. This type of fragmentation is less common in low energy CID processes. The additional ion fragmentation information achievable with higher energy fragmentation techniques can be useful when determining the molecular structure of a compound.
An alternative to CID ion fragramentation is the use of Surface Induced Dissociation to fragment ions of interest. The capability of the Surface Induced Dissociation ion fragmentation technique has been reported for a number of mass analysis applications. Wysocki et. al. J. Am. Soc. for Mass Spectrom, 1992, 3, 27-32 and McCormack et. al., Anal. Chem. 1993, 65, 2859-2872, have demonstrated the use of SID ion fragmentation with quadrupole mass analysis to controllably and reproducibly achieve analytically useful fragmentation information. McCormack et. al. showed that with collisional energies below 100 eV, w and d type ion fragments can be produced from some peptides. Kiloelectronvolt gas phase collisions may be required to achieve similar ion fragmentation. Higher internal energy transfer to an ion can be achieved in SID than with gas phase CID processes allowing the possibility of fragmenting large ions, even those with a large number of degrees of freedom and low numbers of charges. Also, the ion collisional energy distributions can be more tightly controlled with SID when compared with gas phase CID processes. A variety of collision surfaces have been used in SID experiments ranging from metal conductive surfaces such as copper and stainless steel to self-assembled aklyl-monolayer surfaces surfaces such as octadecanethiolate (CH3(CH2) 17SAu), ferrocence terminated self assembled aklyl-monolayer surfaces and fluorinated self-assembled monolayer (F-SAM) surfaces (CF3(CF2)7(CH2)2 SAu). The self-assembled monolayer surfaces tend to reduce the charge loss to the surface during the SID process. Winger et. al. Rev. Sci. Instrum., Vol 63, No. 12, 1992 have reported SID studies using a magnetic sector-dual electric sector-quadrupole (BEEQ) hybrid instrument. They showed kinetic energy distributions of up to +/xe2x88x923 eV for parent and fragment ions leaving a perdeuterated alkyl-monolayer surface after a 25 eV collision. SID collisions have been performed by impacting ions traversing a Time-OF-Flight flight tube onto surfaces positioned in the flight tube and Time-OF-Flight mass to charge analyzing the resulting ion population. Some degree of mass to charge selection prior to SID fragmentation has been achieved by timing the deflection of ions as the initial pulsed ion packet traverses the flight tube. SID surfaces have been positioned in the field free regions and at the bottom of ion reflector lens assemblies in TOF mass analyzers. The resulting TOF mass spectra of the SID fragment ions in these instruments generally have low resolution and low mass measurement accuracy due in part to the broad energy distributions of the SID fragment ions leaving the surface. A population of ions acquiring a kinetic energy spread during its flight path or during a re-acceleration step in an ion reflector degrades TOF performance. The present invention reduces the broad kinetic energy distributions of ions produced by SID fragmentation prior to conducting Time-Of-Flight mass analysis. In the present invention, one or more steps of ion mass to charge selection and CID fragmentation can be conducted prior to performing a SID fragmentation step in the TOF pulsing region.
The present invention relates to the configuration and operation of a Time-Of-Flight mass analyzer in a manner that results in improved TOF performance and range of TOF analytical capability. Ions produced from an ion source are directed to a surface located in the pulsing or first acceleration region of a Time-Of-Flight mass analyzer prior to accelerating the ions located on or near the surface into the Time-Of-Flight tube drift region. Depending on the energy at which the ions are brought to the surface and the surface composition, surface induced dissociation or ion to surface reactions may or may not occur. With low energy or soft-landing conditions, surface induced dissociation may be avoided and the surface serves to reduce the ion kinetic energy distribution and spatial spread in the TOF tube axial direction prior to accelerating the surface collected ions into the Time-Of-Flight tube drift region. The soft landing surface collection or surface xe2x80x9cfocusingxe2x80x9d of ions improves the resolution and duty cycle in Time-Of-Flight mass analysis. Ions entering the TOF first accelerating region are directed onto a surface by applying a reverse potential between the collecting surface and the opposing electrode. Ions collected on the surface are extracted from the surface and or accelerated into the flight tube of a Time-Of-Flight mass analyzer by reversing the electric field between the ion collecting surface and the opposing or extracting electrode or grid. The surface collection and forward acceleration of ion packets can occur at repetition rates exceeding 20 kilohertz allowing TOF pulse repetition rates typically used in gas phase orthogonal pulsing TOF. A low energy laser pulse can be used to release collected ions from surfaces in the presence of an accelerating field. It is desirable to avoid damaging the surface substrate when extracting ions from the surface to reduce unwanted chemical noise in the resulting mass spectra. Frey et. al., Science, 275, 1450, 1997 and Luo et. al., Proceedings of the 45th ASMS Conference on Mass Spectrometry and Allied Topics, 819, 1997 have studied the modification of surface chemistries in F-SAM surfaces. The authors reported using soft-landing of ions on F-SAM surfaces, and after some delay, followed by sputtering of the surface with Xe+ while conducting mass spectrometric analysis. Surface analysis of soft-landed F-SAM surfaces was also conducted using 15-keV Ga+ ion sputtering with TOF mass analysis. Unfortunately, sputtering of ions or neutral molecules damages the surface substrate producing surface substrate related ions. The authors have reported thermally desorbing or evaporating the products of EI generated ions using temperatures ranging from 300xc2x0 to 400xc2x0 C. Thermally desorbed ions were mass to charge analyzed with a quadrupole mass spectrometer. Apparatus and methods configured according to the invention can be used achieve ion extraction from a surface after a surface collection step followed by TOF mass to charge analysis without ion sputtering. Depending on the collecting surface material configured, however, some surface damage may be sustained by the sample ions impacted the surface during a surface induced dissociation fragmentation step.
The magnitude of the reverse electrical potential applied between the surface and the extraction electrode determines the impact energy an ion will have on the surface prior to being forward accelerated into the Time-Of-Flight tube drift region. Ions can be directed to the collecting surface with a soft-landing by applying a low electrical field between the collecting surface and the counter electrode in the TOF pulsing region. Surface induced dissociation of ions can be achieved, prior to pulsing the resulting ion population into the Time-Of-Flight drift region, by increasing the reverse electric field directing the ions to the collecting surface. A variety of ion sources can be configured according to the invention with ability to conduct SID with TOF mass analysis. Ions can be produced directly in the TOF first acceleration region or produced external to the first acceleration region. A time-of-flight configured according to the invention can be selectively operated with or without surface collection, surface induced dissociation or reaction of ions with surfaces prior to Time-Of-Flight mass analysis. The invention retains the ability to conduct existing ionization and TOF analysis techniques. The added ion surface collection and SID fragmentation capability greatly expands the overall analytical range of a Time-Of-Flight mass analyzer. A Time-Of-Flight mass analyzer configured and operated according to the invention can be included in a hybrid mass analyzer enhancing MS/MS or MS/MSn operation and operated with a range of ion sources.
The pulsing or ion extraction region of a Time-Of-Flight mass spectrometer configured with two parallel planar electrodes is configured such that neutral, retarding and ion extraction electric fields can be applied between the two electrodes. The electronics providing voltage to these electrodes is configured such that the neutral, forward and reversed biased electric fields can be rapidly applied by switching between power supplies. In one embodiment of the invention, ions produced in an ion source form an ion beam that enters the pulsing region with the ion beam trajectory substantially parallel to the surfaces of the planar electrodes that define the pulsing region. During the time period when ions are entering the TOT pulsing region, a slight reverse bias field is applied across the two planar electrodes to direct the ions to the collecting electrode surface. In this manner ions are collected on or near the electrode surface for a selected period of time before a forward bias electric field between the planar electrodes is applied, accelerating ions from the ion collecting surface into the TOF tube drift region of the mass analyzer. The primary ion beam is prevented from entering the pulsing region just prior to applying the ion forward accelerating potential to eliminate any ions located in the gap between the electrodes prior to ion acceleration into the TOF tube. The soft-landing continuous collecting of ions on or near the collecting electrode surface, reduces the initial ion beam spatial and energy spread of the primary ion beam prior to acceleration or pulsing of the ion population into the Time-Of-flight tube drift region. Accelerating an ion packet initially shaped as a thin plane at or near the collecting surface into the TOF flight tube improves the resolution and mass accuracy compared with an orthogonally pulsed gas phase primary ion beam. The duty cycle is improved by collecting all m/z value ions with equal efficiency prior to pulsing. The duty cycle of conventional non-trapping continuous beam orthogonal pulsing decreases with the ion mass to charge value. Collecting ions on a surface prior to pulsing reduces the mass to charge duty cycle discrimination in conventional continuous ion beam orthogonal pulsing Time-Of-Flight mass analysis. The duty cycle is also improved because the process of collecting ions on the collecting electrode surface prior to pulsing, serves as a means of integrating ions prior to acceleration into the TOF tube. The ion integration or collection time, however, is limited by space charge buildup on the dielectric or non-conducting collecting surface potentially limiting the number of ions which may be effectively collected prior to pulsing. The space charging at the collecting surface can be controlled to some degree by varying the pulse repetition rate of ions into the TOF mass analyzer. Pulse rates exceeding 20 KHz can be used limited only by the flight time of the mass to charge range of interest.
In another embodiment of the invention, the Time-Of-Flight pulsing region configured for orthogonal pulsing, comprises two parallel planar electrodes, between which neutral, retarding and accelerating fields may be applied. The electric fields can be applied by rapidly switching power supply outputs to one or both electrodes. Ions traveling into the pulsing region with trajectories substantially parallel to the planar electrode surfaces, traverse the pulsing region with a neutral electric field applied between the two planar electrodes. After a selected period of time, a retarding or reverse electric field is applied between the planar electrodes directing the ions located in the pulsing region gap toward the collecting electrode surface. After a preset delay, an accelerating field is applied between the two planar electrodes and the ions are accelerated from the collecting electrode surface into the Time-Of-Flight drift region. One or more ion surface collecting pulses can precede an extraction pulse into the Time-Of-Flight drift region. The magnitude of the reverse or collecting electric field can be set to cause surface induced dissociation (SID) or, alternatively, soft landing of ions when they impact on the surface prior to accelerating the resulting parent or fragment ion population into the Time-Of-Flight drift region.
In another embodiment of the invention, the collecting surface material is configured to minimize charge exchange when an ion impacts the surface. The ion collection time prior to extraction can be set to be sufficiently long to create a space charge near the collecting surface as ions accumulate on or near the surface. This space charge aids in releasing later arriving ions when a rapid reversal of the electric field in the TOF first acceleration region is applied. Alternatively, a laser pulse can be applied to the surface to release ions from the surface in the presence of an accelerating field or with delayed extraction conditions. The laser energy can be set so that sufficient energy is available to release the existing ion population from the surface while minimizing damage to the surface. In some applications, the collecting surface can be heated to facilitate the release of ions from the surface. Collecting surface materials that minimize charge exchange improve ion yield in SID or soft-landing operation resulting in higher TOF sensitivity. The collecting electrode assembly can be comprised of multiple electrode segments with different voltages applied to each segment. Voltages can be applied to a multiple segment electrode during ion collection to direct ions to a particular region of the total electrode surface or to contain ions in a potential well near a dielectric surface as space charge occurs.
In yet another embodiment of the invention, ions are created in the pulsing region of a Time-Of-Flight mass analyzer while maintaining a substantially neutral field between the two electrodes of the pulsing region. The resulting ion population is subsequently directed to the collecting electrode surface prior to pulsing of the ions into the Time-Of-Flight drift region. A specific example of such an embodiment of the invention is the configuration of an Electron Ionization (EI) source in the pulsing region of the Time-Of-Flight mass analyzer. Sample bearing gas is introduced at low pressure into the pulsing region of a Time-Of-Flight mass analyzer with a neutral electric field applied across the pulsing region gap. An electron-emitting filament is turned on with the emitted electrons accelerated into the pulsing region gap to ionize the gas phase sample present. The electron-emitting filament is turned off and a reverse electric field is applied across the pulsing region gap to direct the gaseous ions produced to move toward the collection electrode surface. When the EI generated ions have been collected on or near the collecting electrode surface, an accelerating field is applied across the pulsing region gap to accelerate the ions at or near the collecting surface into the drift region of the Time-Of-Flight mass analyzer. The EI generated ions can be directed to the collecting electrode surface with sufficient energy to cause surface induced dissociation or with low energy to allow a non fragmenting soft-landing. The sample gas may be supplied from a variety of inlet systems including but not limited to a gas chromatograph. Collecting EI generated ions on a surface prior to pulsing into the Time-Of-Flight drift region reduces the ion kinetic energy distribution and spatial spread. This results in higher resolution and mass accuracy Time-Of-Flight mass to charge analysis. If electron ionization occurs in the presence of a low amplitude surface collecting field, the ratio of ionization time to TOF ion acceleration and flight time can be increased resulting in higher overall Time-Of-Flight duty cycle.
In another embodiment of the invention, the pulsing region of a Time-Of-Flight mass analyzer is comprised of two planar electrodes positioned substantially parallel and set a distance apart so as to create a gap between them. This gap is referred to as the TOF first accelerating or pulsing region. The first electrode positioned furthest from the Time-Of-Flight drift region is configured as an ion collecting surface to which ions are directed prior to pulsing into the Time-Of-Flight drift region. A neutral, collecting or extraction electric field can be applied between the two pulsing region electrodes to allow collecting of ions on or near the collecting electrode surface prior to pulsing the spatially compressed ions into the Time-Of-Flight tube drift region. Alternatively, a laser pulse can be applied to the collecting surface to release ions rapidly into an accelerating or delayed extraction field. In this embodiment of the invention, ions generated external to the TOF pulsing region enter the pulsing region in a direction substantially not parallel to the planar electrode surfaces which bound the pulsing region. During the collection period, a reverse electric field is applied across the pulsing region gap to direct ions to the collecting electrode surface. The ions may enter the pulsing region gap with an initial trajectory that is directed either toward or away from the collecting surface. After the ion collection period, the electric field is reversed in the pulsing region and ions on or near the collecting surface are accelerated into the Time-Of-Flight tube for mass to charge analysis. This embodiment of the invention, provides a means for directing ions into a Time-Of-Flight pulsing region from wide variety of ion sources or hybrid instrument electrode geometries with minimal impact on the Time-Of-Flight performance. Depending on the electric field strength applied to direct ions to the collecting surface, ions can impact the collecting surface with a soft-landing or with sufficient energy to cause surface induced dissociation fragmentation. Ions can be collected for a period of time prior to pulsing into the Time-Of-Flight drift region, improving the duty cycle for some applications and operating modes.
In another embodiment of the invention, non-planar electrodes may be configured in the pulsing region. Alternatively, the pulsing or first accelerating region of the time-of-flight mass analyzer may be configured with a three dimensional quadrupole ion trap or a multipole ion guide. One or more surfaces within these non-planar electrode geometries may be configured to serve as a collecting surface or surfaces to reduce the ion population spatial and energy distribution prior to accelerating the ion population into the Time-Of-Flight mass analyzer. Conversely, the non-planar surfaces may be used to fragment ions by SID prior to accelerating the resulting ion population into a TOF tube. When three dimensional quadrupole ion traps or multipole ion guides are configured in the TOF pulsing region, ions released from the surfaces in these electrode geometries may be trapped by the RF electric fields applied to the electrodes prior to extracting the ions into the Time-Of-Flight tube. The gas phase RF trapping of ions after surface ion collection or SID fragmentation is an added step in a TOF mass analysis sequence when compared to the planar electrode geometry configured in the pulsing region. The ion trapping, however, may be used to enhance the analytical capability of the Time-Of-Flight mass analyzer. The same analytical sequences described for planar geometry electrodes configured in the TOF pulsing region can be applied to the non-planar pulsing region electrode configurations to improve Time-Of-Flight performance and analytical capability.
The invention can be configured with a wide range of ion sources including but not limited to, Electron Ionization (EI), Chemical Ionization (CI), Laser Desorption (LD), Matrix Assisted Laser Desorption (MALDI), Electrospray (ES), Atmospheric Pressure Chemical Ionization (APCI), Pyrolysis MS, Inductively Coupled Plasma (ICP), Fast Atom Bombardment (FAB), and Secondary Ion Mass Spectrometry (SIMS). Ions may be subjected to one or more mass to charge selection and/or fragmentation steps prior to entering the Time-Of-Flight pulsing region. The Time-Of-Flight mass analyzer may be configured as a single mass to charge analyzer or as part of a hybrid or tandem instrument. A hybrid Time-Of-Flight mass analyzer configured according to the invention, may include multipole ion guides including quadrupole mass analyzers, magnetic sector, ion trap or additional Time-Of-Flight mass analyzers. According to the invention, analytical sequences can be run that include ion surface induced dissociation alternating with or sequential to gas phase collision induced dissociation in hybrid or tandem mass analyzer configurations. The invention can be used to study ion-surface interactions as well with prior mass to charge selected ion populations. The collecting surface described in the invention may be comprised of a variety of materials including but not limited to metals or other conductor material, semiconductor materials, dielectric materials, Self Assembled Monolayers (SAM) or combinations of materials.